Pub Date : 2024-04-20DOI: 10.12122/j.issn.1673-4254.2024.04.21
S Hu, Z Cheng, M Li, S Gao, D Gao, P Kang
Objective: To explore the impact of diabetes on collateral circulation (CC) development in patients with chronic total coronary occlusion (CTO) and the underlying regulatory mechanism.
Methods: This study was conducted among 87 patients with coronary heart disease (CHD), who had CTO in at least one vessel as confirmed by coronary angiography. Among them 42 patients were found to have a low CC level (Cohen-Rentrop grades 0-1) and 45 had a high CC level (grades 2-3). In the 39 patients with comorbid diabetes mellitus and 48 non-diabetic patients, insulin resistance (IR) levels were compared between the subgroups with different CC levels. The steady-state mode evaluation method was employed for calculating the homeostatic model assessment for insulin resistance index (HOMA-IR) using a mathematical model. During the interventional procedures, collateral and peripheral blood samples were collected from 22 patients for comparison of the metabolites using non-targeted metabolomics analysis.
Results: NT-proBNP levels and LVEF differed significantly between the patients with different CC levels (P<0.05). In non-diabetic patients, HOMA-IR was higher in low CC level group than in high CC level groups. Compared with the non-diabetic patients, the diabetic patients showed 63 upregulated and 48 downregulated metabolites in the collateral blood and 23 upregulated and 14 downregulated metabolites in the peripheral blood. The differential metabolites in the collateral blood were involved in aromatic compound degradation, fatty acid biosynthesis, and steroid degradation pathways; those in the peripheral blood were related with pentose phosphate metabolism, bacterial chemotaxis, hexanoyl-CoA degradation, glycerophospholipid metabolism, and lysine degradation pathways.
Conclusion: The non-diabetic patients with a low level of CC had significant insulin resistance. The degradation pathways of aromatic compounds, fatty acid biosynthesis, and steroid degradation are closely correlated with the development of CC.
目的探讨糖尿病对慢性冠状动脉全闭塞(CTO)患者侧支循环(CC)发展的影响及其潜在的调节机制:研究对象为87名冠心病(CHD)患者,这些患者经冠状动脉造影证实至少有一条血管存在CTO。其中,42 名患者的 CC 水平较低(Cohen-Rentrop 分级 0-1),45 名患者的 CC 水平较高(2-3 级)。在 39 名合并糖尿病的患者和 48 名非糖尿病患者中,比较了不同 CC 水平亚组之间的胰岛素抵抗(IR)水平。在计算胰岛素抵抗指数(HOMA-IR)时,采用了稳态模式评估法,并使用了一个数学模型。在介入治疗过程中,采集了 22 名患者的侧支和外周血样本,利用非靶向代谢组学分析比较代谢物:结果:NT-proBNP 水平和 LVEF 在不同 CC 水平(PC)的患者之间存在显著差异:结论:CC水平低的非糖尿病患者有明显的胰岛素抵抗。芳香族化合物的降解途径、脂肪酸的生物合成和类固醇的降解与 CC 的发生密切相关。
{"title":"[Correlation between insulin resistance and coronary collateral circulation in patients with chronic total coronary occlusion].","authors":"S Hu, Z Cheng, M Li, S Gao, D Gao, P Kang","doi":"10.12122/j.issn.1673-4254.2024.04.21","DOIUrl":"10.12122/j.issn.1673-4254.2024.04.21","url":null,"abstract":"<p><strong>Objective: </strong>To explore the impact of diabetes on collateral circulation (CC) development in patients with chronic total coronary occlusion (CTO) and the underlying regulatory mechanism.</p><p><strong>Methods: </strong>This study was conducted among 87 patients with coronary heart disease (CHD), who had CTO in at least one vessel as confirmed by coronary angiography. Among them 42 patients were found to have a low CC level (Cohen-Rentrop grades 0-1) and 45 had a high CC level (grades 2-3). In the 39 patients with comorbid diabetes mellitus and 48 non-diabetic patients, insulin resistance (IR) levels were compared between the subgroups with different CC levels. The steady-state mode evaluation method was employed for calculating the homeostatic model assessment for insulin resistance index (HOMA-IR) using a mathematical model. During the interventional procedures, collateral and peripheral blood samples were collected from 22 patients for comparison of the metabolites using non-targeted metabolomics analysis.</p><p><strong>Results: </strong>NT-proBNP levels and LVEF differed significantly between the patients with different CC levels (<i>P</i><0.05). In non-diabetic patients, HOMA-IR was higher in low CC level group than in high CC level groups. Compared with the non-diabetic patients, the diabetic patients showed 63 upregulated and 48 downregulated metabolites in the collateral blood and 23 upregulated and 14 downregulated metabolites in the peripheral blood. The differential metabolites in the collateral blood were involved in aromatic compound degradation, fatty acid biosynthesis, and steroid degradation pathways; those in the peripheral blood were related with pentose phosphate metabolism, bacterial chemotaxis, hexanoyl-CoA degradation, glycerophospholipid metabolism, and lysine degradation pathways.</p><p><strong>Conclusion: </strong>The non-diabetic patients with a low level of CC had significant insulin resistance. The degradation pathways of aromatic compounds, fatty acid biosynthesis, and steroid degradation are closely correlated with the development of CC.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11073937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-20DOI: 10.12122/j.issn.1673-4254.2024.04.06
X Duan, J Wei, A Liang, X Ji
Objective: To investigate the effects of different ventilation strategies on intraocular pressure (IOP) and intracranial pressure in patients undergoing spinal surgery in the prone position under general anesthesia.
Methods: Seventy-two patients undergoing prone spinal surgery under general anesthesia between November, 2022 and June, 2023 were equally randomized into two groups to receive routine ventilation (with Vt of 8mL/kg, Fr of 12-15/min, and etCO2 maintained at 35-40 mmHg) or small tidal volume hyperventilation (Vt of 6 mL/kg, Fr of18-20/min, and etCO2 maintained at 30-35 mmHg) during the surgery. IOP of both eyes (measured with a handheld tonometer), optic nerve sheath diameter (ONSD; measured at 3 mm behind the eyeball with bedside real-time ultrasound), circulatory and respiratory parameters of the patients were recorded before anesthesia (T0), immediately after anesthesia induction (T1), immediately after prone positioning (T2), at 2 h during operation (T3), immediately after supine positioning after surgery (T4) and 30 min after the operation (T5).
Results: Compared with those at T1, IOP and ONSD in both groups increased significantly at T3 and T4(P < 0.05). IOP was significantly lower in hyperventilation group than in routine ventilation group at T3 and T4(P < 0.05), and ONSD was significantly lower in hyperventilation group at T4(P < 0.05). IOP was positively correlated with the length of operative time (r=0.779, P < 0.001) and inversely with intraoperative etCO2 at T3(r=-0.248, P < 0.001) and T4(r=-0.251, P < 0.001).ONSD was correlated only with operation time (r=0.561, P < 0.05) and not with IOP (r=0.178, P>0.05 at T3; r=0.165, P>0.05 at T4).
Conclusion: Small tidal volume hyperventilation can relieve the increase of IOP and ONSD during prone spinal surgery under general anesthesia.
{"title":"[Small tidal volume hyperventilation relieves intraocular and intracranial pressure elevation in prone spinal surgery: a randomized controlled trial].","authors":"X Duan, J Wei, A Liang, X Ji","doi":"10.12122/j.issn.1673-4254.2024.04.06","DOIUrl":"10.12122/j.issn.1673-4254.2024.04.06","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effects of different ventilation strategies on intraocular pressure (IOP) and intracranial pressure in patients undergoing spinal surgery in the prone position under general anesthesia.</p><p><strong>Methods: </strong>Seventy-two patients undergoing prone spinal surgery under general anesthesia between November, 2022 and June, 2023 were equally randomized into two groups to receive routine ventilation (with Vt of 8mL/kg, Fr of 12-15/min, and etCO<sub>2</sub> maintained at 35-40 mmHg) or small tidal volume hyperventilation (Vt of 6 mL/kg, Fr of18-20/min, and etCO<sub>2</sub> maintained at 30-35 mmHg) during the surgery. IOP of both eyes (measured with a handheld tonometer), optic nerve sheath diameter (ONSD; measured at 3 mm behind the eyeball with bedside real-time ultrasound), circulatory and respiratory parameters of the patients were recorded before anesthesia (T<sub>0</sub>), immediately after anesthesia induction (T<sub>1</sub>), immediately after prone positioning (T<sub>2</sub>), at 2 h during operation (T<sub>3</sub>), immediately after supine positioning after surgery (T<sub>4</sub>) and 30 min after the operation (T<sub>5</sub>).</p><p><strong>Results: </strong>Compared with those at T<sub>1</sub>, IOP and ONSD in both groups increased significantly at T<sub>3</sub> and T<sub>4</sub>(<i>P</i> < 0.05). IOP was significantly lower in hyperventilation group than in routine ventilation group at T<sub>3</sub> and T<sub>4</sub>(<i>P</i> < 0.05), and ONSD was significantly lower in hyperventilation group at T<sub>4</sub>(<i>P</i> < 0.05). IOP was positively correlated with the length of operative time (<i>r</i>=0.779, <i>P</i> < 0.001) and inversely with intraoperative etCO<sub>2</sub> at T<sub>3</sub>(<i>r</i>=-0.248, <i>P</i> < 0.001) and T<sub>4</sub>(<i>r</i>=-0.251, <i>P</i> < 0.001).ONSD was correlated only with operation time (<i>r</i>=0.561, <i>P</i> < 0.05) and not with IOP (<i>r</i>=0.178, <i>P</i>>0.05 at T<sub>3</sub>; <i>r</i>=0.165, <i>P</i>>0.05 at T<sub>4</sub>).</p><p><strong>Conclusion: </strong>Small tidal volume hyperventilation can relieve the increase of IOP and ONSD during prone spinal surgery under general anesthesia.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11073951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-20DOI: 10.12122/j.issn.1673-4254.2024.04.01
Yiming Sun, Ailan Huang, Zhi Zhao, Chen Song, Guihua Lai
Objective: To investigate immunogenic and toxic effects of graphene oxide (GO) nanoparticles in mouse skeletal muscles and in human blood in vitro.
Methods: GO nanoparticles prepared using a probe sonicator were supended in deionized H2O or PBS, and particle size and surface charge of the nanoparticles were measured with dynamic light scattering (DLS). Different concentrations (0.5, 1.0 and 2.0 mg/mL) of GO suspension or PBS were injected at multiple sites in the gastrocnemius muscle (GN) of C57BL/6 mice, and inflammatory response and immune cell infiltrations were detected with HE and immunofluorescence staining. We also examined the effects of GO nanoparticles on human red blood cell (RBC) morphology, hemolysis and blood coagulation using scanning electron microscope (SEM), spectrophotometry, and thromboelastography (TEG).
Results: GO nanoparticles suspended in PBS exhibited better colloidal dispersity, stability and surface charge effects than those in deionized H2O. In mouse GNs, injection of GO suspensions dose- and time-dependently resulted in sustained muscular inflammation and myofiber degeneration at the injection sites, which lasted till 8 weeks after the injection; immunofluorescence staining revealed obvious infiltration of monocytes, macrophages, dendritic cells and CD4+ T cells around the injection sites in mouse GNs. In human RBCs, incubation with GO suspensions at 0.2, 2.0 and 20 mg/mL, but not at 0.002 or 0.02 mg/mL, caused significant alterations of cell morphology and hemolysis. TEG analysis showed significant abnormalities of blood coagulation parameters following treatment with high concentrations of GO.
Conclusion: GO nanoparticles can induce sustained inflammatory and immunological responses in mouse GNs and cause RBC hemolysis and blood coagulation impairment, suggesting its muscular toxicity and hematotoxicity at high concentrations.
目的研究氧化石墨烯(GO)纳米颗粒在小鼠骨骼肌和人体血液中的体外免疫原性和毒性效应:用探针声波发生器制备 GO 纳米粒子,将其置于去离子水或 PBS 中,用动态光散射法(DLS)测量纳米粒子的粒径和表面电荷。在 C57BL/6 小鼠腓肠肌(GN)的多个部位注射不同浓度(0.5、1.0 和 2.0 mg/mL)的 GO 悬浮液或 PBS,用 HE 和免疫荧光染色法检测炎症反应和免疫细胞浸润。我们还使用扫描电子显微镜(SEM)、分光光度计和血栓弹力图(TEG)研究了 GO 纳米粒子对人类红细胞(RBC)形态、溶血和血液凝固的影响:结果:与去离子水相比,悬浮在 PBS 中的 GO 纳米粒子具有更好的胶体分散性、稳定性和表面电荷效应。在小鼠GNs中,注射GO悬浮液可导致注射部位持续的肌肉炎症和肌纤维变性,这种情况在注射后持续8周;免疫荧光染色显示小鼠GNs注射部位周围有明显的单核细胞、巨噬细胞、树突状细胞和CD4+T细胞浸润。在人红细胞中,与 0.2、2.0 和 20 毫克/毫升(而不是 0.002 或 0.02 毫克/毫升)的 GO 悬浮液一起孵育会导致细胞形态和溶血的显著改变。TEG分析表明,使用高浓度的GO处理后,血液凝固参数出现明显异常:结论:GO 纳米粒子可诱导小鼠 GN 产生持续的炎症和免疫反应,并导致 RBC 溶血和血液凝固障碍,这表明高浓度 GO 纳米粒子具有肌肉毒性和血液毒性。
{"title":"[Immunogenic and toxic effects of graphene oxide nanoparticles in mouse skeletal muscles and human red blood cells].","authors":"Yiming Sun, Ailan Huang, Zhi Zhao, Chen Song, Guihua Lai","doi":"10.12122/j.issn.1673-4254.2024.04.01","DOIUrl":"10.12122/j.issn.1673-4254.2024.04.01","url":null,"abstract":"<p><strong>Objective: </strong>To investigate immunogenic and toxic effects of graphene oxide (GO) nanoparticles in mouse skeletal muscles and in human blood <i>in vitro</i>.</p><p><strong>Methods: </strong>GO nanoparticles prepared using a probe sonicator were supended in deionized H<sub>2</sub>O or PBS, and particle size and surface charge of the nanoparticles were measured with dynamic light scattering (DLS). Different concentrations (0.5, 1.0 and 2.0 mg/mL) of GO suspension or PBS were injected at multiple sites in the gastrocnemius muscle (GN) of C57BL/6 mice, and inflammatory response and immune cell infiltrations were detected with HE and immunofluorescence staining. We also examined the effects of GO nanoparticles on human red blood cell (RBC) morphology, hemolysis and blood coagulation using scanning electron microscope (SEM), spectrophotometry, and thromboelastography (TEG).</p><p><strong>Results: </strong>GO nanoparticles suspended in PBS exhibited better colloidal dispersity, stability and surface charge effects than those in deionized H<sub>2</sub>O. In mouse GNs, injection of GO suspensions dose- and time-dependently resulted in sustained muscular inflammation and myofiber degeneration at the injection sites, which lasted till 8 weeks after the injection; immunofluorescence staining revealed obvious infiltration of monocytes, macrophages, dendritic cells and CD4<sup>+</sup> T cells around the injection sites in mouse GNs. In human RBCs, incubation with GO suspensions at 0.2, 2.0 and 20 mg/mL, but not at 0.002 or 0.02 mg/mL, caused significant alterations of cell morphology and hemolysis. TEG analysis showed significant abnormalities of blood coagulation parameters following treatment with high concentrations of GO.</p><p><strong>Conclusion: </strong>GO nanoparticles can induce sustained inflammatory and immunological responses in mouse GNs and cause RBC hemolysis and blood coagulation impairment, suggesting its muscular toxicity and hematotoxicity at high concentrations.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11073950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.12122/j.issn.1673-4254.2024.03.11
H Bao, S Wang, M Lü, Y Wang, P Jiang, X Li
Objective: To investigate the effects of α7 nicotinic acetylcholine receptor (nAChR) agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice.
Methods: Forty obese C57BL/6J mice were randomized into high-fat feeding group, β3-adrenoceptor agonist-treated model group, α7 nAChR agonist group, and α7 nAChR inhibitor group (n=10), with another 10 mice with normal feeding as the blank control group. White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes. The expression levels of TNF-α, IL-1β, IL-10 and TGF-β in the white adipose tissue were determined by ELISA, and the mRNA levels of iNOS, Arg1, UCP-1, PRDM-16 and PGC-1α were detected using RT-qPCR. Western blotting was performed to detect the expression levels of NF-κB P65, p-JAK2, p-STAT3 in the white adipose tissue.
Results: Compared with those in the blank control group, the mice with high-fat feeding showed significantly increased body weight, more fat vacuoles in the white adipose tissue, increased volume of lipid droplets in the adipocytes, upregulated iNOS mRNA expression and protein expression of TNF-α and IL-1β, and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins (P < 0.01). Treatment with α7 nAChR significantly reduced mRNA levels of PRDM-16, PGC-1α and UCP-1, lowered TNF-α and IL-1β expressions, increased IL-10 and TGF-β expressions, and reduced M1/M2 macrophage ratio in the white adipose tissues (P < 0.05 or 0.01).
Conclusion: Activation of α7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist, promotes transformation of M1 to M2 macrophages, reduces inflammatory response in white adipose tissue, and promote beige adipogenesis and thermogenesis in obese mice.
{"title":"[Activation of <i>α</i>7 nAChR improves white fat homeostasis and promotes beige adipogenesis and thermogenesis in obese mice].","authors":"H Bao, S Wang, M Lü, Y Wang, P Jiang, X Li","doi":"10.12122/j.issn.1673-4254.2024.03.11","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2024.03.11","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the effects of <i>α</i>7 nicotinic acetylcholine receptor (nAChR) agonist on β3-adrenoceptor agonist-induced impairment of white fat homeostasis and beige adipose formation and heat production in obese mice.</p><p><strong>Methods: </strong>Forty obese C57BL/6J mice were randomized into high-fat feeding group, β3-adrenoceptor agonist-treated model group, <i>α</i>7 nAChR agonist group, and <i>α</i>7 nAChR inhibitor group (<i>n</i>=10), with another 10 mice with normal feeding as the blank control group. White adipose tissue from the epididymis of the mice were sampled for HE staining of the adipocytes. The expression levels of TNF-<i>α</i>, IL-1β, IL-10 and TGF-β in the white adipose tissue were determined by ELISA, and the mRNA levels of iNOS, Arg1, UCP-1, PRDM-16 and PGC-1<i>α</i> were detected using RT-qPCR. Western blotting was performed to detect the expression levels of NF-κB P65, p-JAK2, p-STAT3 in the white adipose tissue.</p><p><strong>Results: </strong>Compared with those in the blank control group, the mice with high-fat feeding showed significantly increased body weight, more fat vacuoles in the white adipose tissue, increased volume of lipid droplets in the adipocytes, upregulated iNOS mRNA expression and protein expression of TNF-<i>α</i> and IL-1β, and lowered expression of Arg-1 mRNA and IL-10 and TGF-β proteins (<i>P</i> < 0.01). Treatment with <i>α</i>7 nAChR significantly reduced mRNA levels of PRDM-16, PGC-1<i>α</i> and UCP-1, lowered TNF-<i>α</i> and IL-1β expressions, increased IL-10 and TGF-β expressions, and reduced M1/M2 macrophage ratio in the white adipose tissues (<i>P</i> < 0.05 or 0.01).</p><p><strong>Conclusion: </strong>Activation of <i>α</i>7 nAchR improves white adipose tissue homeostasis impairment induced by β3 agonist, promotes transformation of M1 to M2 macrophages, reduces inflammatory response in white adipose tissue, and promote beige adipogenesis and thermogenesis in obese mice.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.12122/j.issn.1673-4254.2024.03.10
Y Ge, J Li, H Liang, L Hou, L Zuo, Z Chen, J Lu, X Zhao, J Liang, L Peng, J Bao, J Duan, L Liu, K Mao, Z Zeng, H Hu, Z Chen
Objective: To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO).
Methods: We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January, 2015 and January, 2022 using a convenience sampling method. The patients were divided into a derivation cohort (201 cases) and a validation cohort (101 cases). Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients, based on which a risk prediction model was established in the form of a nomogram. The receiver operator characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the discrimination ability, calibration and clinical validity of this model.
Results: The in-hospital mortality risk prediction model was established based the risk factors including hypertension (OR=3.694, 95% CI: 1.582-8.621), continuous renal replacement therapy (OR=9.661, 95%CI: 4.103-22.745), elevated Na2 + level (OR=1.048, 95% CI: 1.003-1.095) and increased hemoglobin level (OR=0.987, 95% CI: 0.977-0.998). In the derivation cohort, the area under the ROC curve (AUC) of this model was 0.829 (95% CI: 0.770-0.889), greater than those of the 4 single factors (all AUC < 0.800), APACHE II Score (AUC=0.777, 95% CI: 0.714-0.840) and the SOFA Score (AUC=0.721, 95% CI: 0.647-0.796). The results of internal validation showed that the AUC of the model was 0.774 (95% CI: 0.679-0.869), and the goodness of fit test showed a good fitting of this model (χ2=4.629, P>0.05).
Conclusion: The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation, calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system, and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.
{"title":"[Construction and validation of an in-hospital mortality risk prediction model for patients receiving VA-ECMO: a retrospective multi-center case-control study].","authors":"Y Ge, J Li, H Liang, L Hou, L Zuo, Z Chen, J Lu, X Zhao, J Liang, L Peng, J Bao, J Duan, L Liu, K Mao, Z Zeng, H Hu, Z Chen","doi":"10.12122/j.issn.1673-4254.2024.03.10","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2024.03.10","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO).</p><p><strong>Methods: </strong>We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January, 2015 and January, 2022 using a convenience sampling method. The patients were divided into a derivation cohort (201 cases) and a validation cohort (101 cases). Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients, based on which a risk prediction model was established in the form of a nomogram. The receiver operator characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the discrimination ability, calibration and clinical validity of this model.</p><p><strong>Results: </strong>The in-hospital mortality risk prediction model was established based the risk factors including hypertension (OR=3.694, 95% <i>CI</i>: 1.582-8.621), continuous renal replacement therapy (OR=9.661, 95%<i>CI</i>: 4.103-22.745), elevated Na2 + level (OR=1.048, 95% <i>CI</i>: 1.003-1.095) and increased hemoglobin level (OR=0.987, 95% <i>CI</i>: 0.977-0.998). In the derivation cohort, the area under the ROC curve (AUC) of this model was 0.829 (95% <i>CI</i>: 0.770-0.889), greater than those of the 4 single factors (all AUC < 0.800), APACHE II Score (AUC=0.777, 95% <i>CI</i>: 0.714-0.840) and the SOFA Score (AUC=0.721, 95% <i>CI</i>: 0.647-0.796). The results of internal validation showed that the AUC of the model was 0.774 (95% <i>CI</i>: 0.679-0.869), and the goodness of fit test showed a good fitting of this model (χ<sup>2</sup>=4.629, <i>P</i>>0.05).</p><p><strong>Conclusion: </strong>The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation, calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system, and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140866212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.12122/j.issn.1673-4254.2024.03.01
G Xu, A Gao, B Cong
Objective: To investigate the role of Rho/ROCK signaling pathway in mediating restraint stress-induced blood-brain barrier (BBB) injury in the amygdala of rats.
Methods: Sixty male SD rats were randomized equally into control group (with food and water deprivation for 6 h per day), restraint stress group (with restraint for 6 h per day), stress + fasudil treatment (administered by intraperitoneal injection at 1 mg/100 g 30 min before the 6-h restraint) group, and fasudil treatment alone group. The elevated plus-maze test was used to detect behavioral changes of the rats, serum corticosterone and S100B levels were determined with ELISA, and Evans Blue leakage in the brain tissue was examined to evaluate the changes in BBB permeability. The changes in expression levels of tight junction proteins in the amygdala were detected using immunofluorescence assay and Western blotting, and Rho/ROCK pathway activation was detected by Pull-down test and Western blotting. Ultrastructural changes of the cerebral microvascular endothelial cells were observed using transmission electron microscopy.
Results: Compared with those in the control group, the rats in restrain stress group and stress+fasudil group showed obvious anxiety-like behavior with significantly increased serum corticosterone level (P<0.001). Compared with those in the control group and stress+fasudil group, the rat models of restrain stress showed more obvious Evans Blue leakage and higher S100B expression (P<0.01) but lower expressions of tight junction proteins in the amygdala. Pull-down test and Western blotting confirmed that the expression levels of RhoA-GTP, ROCK2 and P-MLC 2 were significantly higher in stress group than in the control group and stress + fasudil group (P<0.05). Transmission electron microscopy revealed obvious ultrastructural changes in the cerebral microvascular endothelial cells in the rat models of restrain stress.
Conclusion: Restraint stress induces BBB injury in the amygdala of rats by activating the Rho/ROCK signaling pathway.
目的研究Rho/ROCK信号通路在介导束缚应激诱导的大鼠杏仁核血脑屏障(BBB)损伤中的作用:将60只雄性SD大鼠随机平均分为对照组(每天断食断水6小时)、束缚应激组(每天束缚6小时)、应激+法舒地尔治疗组(束缚6小时前30分钟腹腔注射1 mg/100 g)和单独法舒地尔治疗组。采用高架迷宫试验检测大鼠的行为变化,用酶联免疫吸附法测定血清皮质酮和S100B水平,并检测脑组织中伊文思蓝渗漏以评估BBB通透性的变化。用免疫荧光检测法和 Western 印迹法检测杏仁核中紧密连接蛋白表达水平的变化,用 Pull-down 试验和 Western 印迹法检测 Rho/ROCK 通路的激活情况。透射电子显微镜观察脑微血管内皮细胞的超微结构变化:结果:与对照组相比,束缚应激组和应激+法舒地尔组大鼠表现出明显的焦虑样行为,血清皮质酮水平显著升高(PPP结论:束缚应激和应激+法舒地尔组大鼠均表现出明显的焦虑样行为,血清皮质酮水平显著升高(PPP):束缚应激通过激活 Rho/ROCK 信号通路诱导大鼠杏仁核 BBB 损伤。
{"title":"[Restraint stress induces blood-brain barrier injury in rat amygdala by activating the Rho/ROCK signaling pathway].","authors":"G Xu, A Gao, B Cong","doi":"10.12122/j.issn.1673-4254.2024.03.01","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2024.03.01","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role of Rho/ROCK signaling pathway in mediating restraint stress-induced blood-brain barrier (BBB) injury in the amygdala of rats.</p><p><strong>Methods: </strong>Sixty male SD rats were randomized equally into control group (with food and water deprivation for 6 h per day), restraint stress group (with restraint for 6 h per day), stress + fasudil treatment (administered by intraperitoneal injection at 1 mg/100 g 30 min before the 6-h restraint) group, and fasudil treatment alone group. The elevated plus-maze test was used to detect behavioral changes of the rats, serum corticosterone and S100B levels were determined with ELISA, and Evans Blue leakage in the brain tissue was examined to evaluate the changes in BBB permeability. The changes in expression levels of tight junction proteins in the amygdala were detected using immunofluorescence assay and Western blotting, and Rho/ROCK pathway activation was detected by Pull-down test and Western blotting. Ultrastructural changes of the cerebral microvascular endothelial cells were observed using transmission electron microscopy.</p><p><strong>Results: </strong>Compared with those in the control group, the rats in restrain stress group and stress+fasudil group showed obvious anxiety-like behavior with significantly increased serum corticosterone level (<i>P</i><0.001). Compared with those in the control group and stress+fasudil group, the rat models of restrain stress showed more obvious Evans Blue leakage and higher S100B expression (<i>P</i><0.01) but lower expressions of tight junction proteins in the amygdala. Pull-down test and Western blotting confirmed that the expression levels of RhoA-GTP, ROCK2 and P-MLC 2 were significantly higher in stress group than in the control group and stress + fasudil group (<i>P</i><0.05). Transmission electron microscopy revealed obvious ultrastructural changes in the cerebral microvascular endothelial cells in the rat models of restrain stress.</p><p><strong>Conclusion: </strong>Restraint stress induces BBB injury in the amygdala of rats by activating the Rho/ROCK signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.12122/j.issn.1673-4254.2024.03.06
H Chen, Z Li, M Wang, L Lu, Q Tang, L Luo
Objective: To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma (HCC) microenvironment and its impact on proliferation and stemness of HCC cells.
Methods: TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC. Specific expression patterns of UBE2S, intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website. We further examined UBE2S expressions in clinical samples of HCC tissues, HCC cells and T cells using immunohistochemistry and immunofluorescence staining. We also tested the effects of UBE2S knockdown on stemness of HCC-LM3 and HepG2 cells using clone formation experiments and sphere formation assay.
Results: Analysis based on TCGA database suggested significant overexpression of UBE2S in both paired and non-paired tumor tissues (P < 0.001), and its transcriptional level increased with tumor grades. The methylation level of UBE2S promoter was significantly decreased in HCC (P < 0.001), and its transcription level increased obviously in HCC with TP53 mutation (P < 0.001). Analysis of CPTAC database also demonstrated overexpression of UBE2S protein in HCC tissues (P < 0.001). Three prognostic models suggested that HCC patients with high UBE2S expression had poorer prognosis (P < 0.001). Single-cell sequencing data analysis revealed high expressions of UBE2S in T cells and high intensities of interaction between endothelial cells, epithelial cells and fibroblasts in HCC microenvironment. Immunohistochemistry and immunofluorescence staining demonstrated high UBE2S expressions in clinical samples of HCC tissues, HCC cells and T cells. In HCC-LM3 and HepG2 cells, UBE2S knockdown significantly inhibited cell clone formation and tumor sphere formation (P < 0.05).
Conclusion: UBE2S is highly expressed in T cells in HCC microenvironment in close correlation with a poor prognosis. High UBE2S expression promotes the stemness of HCC cells.
{"title":"[High expression of UBE2S promotes progression of hepatocellular carcinoma by increasing cancer cell stemness].","authors":"H Chen, Z Li, M Wang, L Lu, Q Tang, L Luo","doi":"10.12122/j.issn.1673-4254.2024.03.06","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2024.03.06","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the expression of the ubiquitination enzyme UBE2S in different cell types in hepatocellular carcinoma (HCC) microenvironment and its impact on proliferation and stemness of HCC cells.</p><p><strong>Methods: </strong>TCGA and CPTAC database were used to analyze the transcriptional and promoter methylation levels and protein expressions of UBE2S in HCC. Specific expression patterns of UBE2S, intercellular communication and key transcription factors in different cell types were analyzed based on single-cell sequencing data from TISCH website. We further examined UBE2S expressions in clinical samples of HCC tissues, HCC cells and T cells using immunohistochemistry and immunofluorescence staining. We also tested the effects of UBE2S knockdown on stemness of HCC-LM3 and HepG2 cells using clone formation experiments and sphere formation assay.</p><p><strong>Results: </strong>Analysis based on TCGA database suggested significant overexpression of UBE2S in both paired and non-paired tumor tissues (<i>P</i> < 0.001), and its transcriptional level increased with tumor grades. The methylation level of UBE2S promoter was significantly decreased in HCC (<i>P</i> < 0.001), and its transcription level increased obviously in HCC with TP53 mutation (<i>P</i> < 0.001). Analysis of CPTAC database also demonstrated overexpression of UBE2S protein in HCC tissues (<i>P</i> < 0.001). Three prognostic models suggested that HCC patients with high UBE2S expression had poorer prognosis (<i>P</i> < 0.001). Single-cell sequencing data analysis revealed high expressions of UBE2S in T cells and high intensities of interaction between endothelial cells, epithelial cells and fibroblasts in HCC microenvironment. Immunohistochemistry and immunofluorescence staining demonstrated high UBE2S expressions in clinical samples of HCC tissues, HCC cells and T cells. In HCC-LM3 and HepG2 cells, UBE2S knockdown significantly inhibited cell clone formation and tumor sphere formation (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>UBE2S is highly expressed in T cells in HCC microenvironment in close correlation with a poor prognosis. High UBE2S expression promotes the stemness of HCC cells.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.12122/j.issn.1673-4254.2024.03.04
S Li, S Yu, Y Mu, K Wang, Y Liu, M Zhang
Objective: To investigate the protective effect of metformin against PM2.5-induced functional impairment of placental trophoblasts and explore the underlying mechanism.
Methods: Sixteen pregnant Kunming mice were randomly assigned into two groups (n=8) for intratracheal instillation of PBS or PM2.5 suspension at 1.5, 7.5, and 12.5 days of gestation. The pregnancy outcome of the mice was observed, and placental zonal structure and vascular density of the labyrinth area were examined with HE staining, followed by detection of ferroptosis-related indexes in the placenta. In cultured human trophoblasts (HTR8/SVneo cells), the effects of PM2.5 exposure and treatment with metformin on cell viability, proliferation, migration, invasion, and tube formation ability were evaluated using CCK8 assay, EDU staining, wound healing assay, Transwell experiment, and tube formation experiment; the cellular expressions of ferroptosis-related proteins were analyzed using ELISA and Western blotting.
Results: M2.5 exposure of the mice during pregnancy resulted in significantly decreased weight and number of the fetuses and increased fetal mortality with a reduced placental weight (all P<0.001). PM2.5 exposure also caused obvious impairment of the placental structure and trophoblast ferroptosis. In cultured HTR8/SVneo cells, PM2.5 significantly inhibited proliferation, migration, invasion, and angiogenesis of the cells by causing ferroptosis. Metformin treatment obviously attenuated PM2.5-induced inhibition of proliferation, migration, invasion, and angiogenesis of the cells, and effectively reversed PM2.5-induced ferroptosis in the trophoblasts as shown by significantly increased intracellular GSH level and SOD activity, reduced MDA and Fe2+ levels, and upregulated GPX4 and SLC7A11 protein expression (P<0.05 or 0.01).
Conclusion: PM2.5 exposure during pregnancy causes adverse pregnancy outcomes and ferroptosis and functional impairment of placental trophoblasts in mice, and metformin can effectively alleviate PM2.5-induced trophoblast impairment.
目的研究二甲双胍对PM2.5诱导的胎盘滋养细胞功能损伤的保护作用,并探讨其潜在机制:16只妊娠昆明小鼠随机分为两组(n=8),分别在妊娠1.5、7.5和12.5天气管内灌注PBS或PM2.5悬浮液。观察小鼠的妊娠结局,用 HE 染色法检查胎盘带状结构和迷宫区的血管密度,然后检测胎盘中与铁败坏相关的指标。在培养的人滋养细胞(HTR8/SVneo细胞)中,使用CCK8检测法、EDU染色法、伤口愈合检测法、Transwell实验和管形成实验评估了PM2.5暴露和二甲双胍处理对细胞活力、增殖、迁移、侵袭和管形成能力的影响;使用ELISA和Western印迹法分析了铁变态反应相关蛋白的细胞表达:结果:妊娠期小鼠暴露于M2.5会导致胎儿体重和胎儿数量显著下降,胎儿死亡率增加,胎盘重量减少(所有P2+水平),GPX4和SLC7A11蛋白表达上调(PConclusion:妊娠期暴露于PM2.5会导致不良妊娠结局以及小鼠胎盘滋养细胞的铁变态反应和功能损伤,而二甲双胍能有效缓解PM2.5诱导的滋养细胞损伤。
{"title":"[Metformin ameliorates PM2.5-induced functional impairment of placental trophoblasts by inhibiting ferroptosis].","authors":"S Li, S Yu, Y Mu, K Wang, Y Liu, M Zhang","doi":"10.12122/j.issn.1673-4254.2024.03.04","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2024.03.04","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the protective effect of metformin against PM2.5-induced functional impairment of placental trophoblasts and explore the underlying mechanism.</p><p><strong>Methods: </strong>Sixteen pregnant Kunming mice were randomly assigned into two groups (<i>n</i>=8) for intratracheal instillation of PBS or PM2.5 suspension at 1.5, 7.5, and 12.5 days of gestation. The pregnancy outcome of the mice was observed, and placental zonal structure and vascular density of the labyrinth area were examined with HE staining, followed by detection of ferroptosis-related indexes in the placenta. In cultured human trophoblasts (HTR8/SVneo cells), the effects of PM2.5 exposure and treatment with metformin on cell viability, proliferation, migration, invasion, and tube formation ability were evaluated using CCK8 assay, EDU staining, wound healing assay, Transwell experiment, and tube formation experiment; the cellular expressions of ferroptosis-related proteins were analyzed using ELISA and Western blotting.</p><p><strong>Results: </strong>M2.5 exposure of the mice during pregnancy resulted in significantly decreased weight and number of the fetuses and increased fetal mortality with a reduced placental weight (all <i>P</i><0.001). PM2.5 exposure also caused obvious impairment of the placental structure and trophoblast ferroptosis. In cultured HTR8/SVneo cells, PM2.5 significantly inhibited proliferation, migration, invasion, and angiogenesis of the cells by causing ferroptosis. Metformin treatment obviously attenuated PM2.5-induced inhibition of proliferation, migration, invasion, and angiogenesis of the cells, and effectively reversed PM2.5-induced ferroptosis in the trophoblasts as shown by significantly increased intracellular GSH level and SOD activity, reduced MDA and Fe<sup>2+</sup> levels, and upregulated GPX4 and SLC7A11 protein expression (<i>P</i><0.05 or 0.01).</p><p><strong>Conclusion: </strong>PM2.5 exposure during pregnancy causes adverse pregnancy outcomes and ferroptosis and functional impairment of placental trophoblasts in mice, and metformin can effectively alleviate PM2.5-induced trophoblast impairment.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140867775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.12122/j.issn.1673-4254.2024.03.21
K Long, D Weng, J Geng, Y Lu, Z Zhou, L Cao
Objective: To develop a multi-modal deep learning method for automatic classification of immune-mediated glomerular diseases based on images of optical microscopy (OM), immunofluorescence microscopy (IM), and transmission electron microscopy (TEM).
Methods: We retrospectively collected the pathological images from 273 patients and constructed a multi-modal multi- instance model for classification of 3 immune-mediated glomerular diseases, namely immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN). This model adopts an instance-level multi-instance learning (I-MIL) method to select the TEM images for multi-modal feature fusion with the OM images and IM images of the same patient. By comparing this model with unimodal and bimodal models, we explored different combinations of the 3 modalities and the optimal methods for modal feature fusion.
Results: The multi-modal multi-instance model combining OM, IM, and TEM images had a disease classification accuracy of (88.34±2.12)%, superior to that of the optimal unimodal model [(87.08±4.25)%] and that of the optimal bimodal model [(87.92±3.06)%].
Conclusion: This multi- modal multi- instance model based on OM, IM, and TEM images can achieve automatic classification of immune-mediated glomerular diseases with a good classification accuracy.
目的开发一种基于光学显微镜(OM)、免疫荧光显微镜(IM)和透射电子显微镜(TEM)图像的多模态深度学习方法,用于免疫介导的肾小球疾病的自动分类:我们回顾性地收集了273名患者的病理图像,并构建了一个多模态多实例模型,用于对免疫球蛋白A肾病(IgAN)、膜性肾病(MN)和狼疮性肾炎(LN)这3种免疫介导的肾小球疾病进行分类。该模型采用实例级多实例学习(I-MIL)方法,选择 TEM 图像与同一患者的 OM 图像和 IM 图像进行多模态特征融合。通过将该模型与单模态和双模态模型进行比较,我们探索了三种模态的不同组合以及模态特征融合的最佳方法:结合 OM、IM 和 TEM 图像的多模态多实例模型的疾病分类准确率为 (88.34±2.12)%,优于最佳单模态模型[(87.08±4.25)%]和最佳双模态模型[(87.92±3.06)%]:这种基于OM、IM和TEM图像的多模态多实例模型可实现免疫介导的肾小球疾病的自动分类,且分类准确率较高。
{"title":"[Automatic classification of immune-mediated glomerular diseases based on multi-modal multi-instance learning].","authors":"K Long, D Weng, J Geng, Y Lu, Z Zhou, L Cao","doi":"10.12122/j.issn.1673-4254.2024.03.21","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2024.03.21","url":null,"abstract":"<p><strong>Objective: </strong>To develop a multi-modal deep learning method for automatic classification of immune-mediated glomerular diseases based on images of optical microscopy (OM), immunofluorescence microscopy (IM), and transmission electron microscopy (TEM).</p><p><strong>Methods: </strong>We retrospectively collected the pathological images from 273 patients and constructed a multi-modal multi- instance model for classification of 3 immune-mediated glomerular diseases, namely immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN). This model adopts an instance-level multi-instance learning (I-MIL) method to select the TEM images for multi-modal feature fusion with the OM images and IM images of the same patient. By comparing this model with unimodal and bimodal models, we explored different combinations of the 3 modalities and the optimal methods for modal feature fusion.</p><p><strong>Results: </strong>The multi-modal multi-instance model combining OM, IM, and TEM images had a disease classification accuracy of (88.34±2.12)%, superior to that of the optimal unimodal model [(87.08±4.25)%] and that of the optimal bimodal model [(87.92±3.06)%].</p><p><strong>Conclusion: </strong>This multi- modal multi- instance model based on OM, IM, and TEM images can achieve automatic classification of immune-mediated glomerular diseases with a good classification accuracy.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-20DOI: 10.12122/j.issn.1673-4254.2024.03.16
F Zhang, L Fan, X Kang, H Wei, L Li
Objective: To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma.
Methods: We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP. qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines (OE-19, TE-7, Bic-1, Flo-1, SK-GT-4, and BE-3) and a normal esophageal epithelial cell line (HET-1A). OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection, and the changes in proliferation, migration and invasion of the cells were evaluated using Cell Counting Kit-8 (CCK-8) assay and Transwell migration/invasion assay. The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting. The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice.
Results: The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells. LINC00626 knockdown obviously inhibited the proliferation, migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice, while overexpression of LINC00626 produced the opposite effects. In esophageal adenocarcinoma cells, LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3.
Conclusion: High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.
{"title":"[High LINC00626 expression promotes esophagogastric junction adenocarcinoma metastasis: the mediating role of the JAK1/STAT3/KHSRP axis].","authors":"F Zhang, L Fan, X Kang, H Wei, L Li","doi":"10.12122/j.issn.1673-4254.2024.03.16","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2024.03.16","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma.</p><p><strong>Methods: </strong>We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP. qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines (OE-19, TE-7, Bic-1, Flo-1, SK-GT-4, and BE-3) and a normal esophageal epithelial cell line (HET-1A). OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection, and the changes in proliferation, migration and invasion of the cells were evaluated using Cell Counting Kit-8 (CCK-8) assay and Transwell migration/invasion assay. The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting. The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice.</p><p><strong>Results: </strong>The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells. LINC00626 knockdown obviously inhibited the proliferation, migration and invasion of esophageal adenocarcinoma cells <i>in vitro</i> and decreased their tumor formation and lung metastasis abilities in nude mice, while overexpression of LINC00626 produced the opposite effects. In esophageal adenocarcinoma cells, LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3.</p><p><strong>Conclusion: </strong>High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.</p>","PeriodicalId":18962,"journal":{"name":"Nan fang yi ke da xue xue bao = Journal of Southern Medical University","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11006707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}